Cord Blood Transplantation Research Articles

Comparative outcomes of various transplantation platforms, highlighting haploidentical transplants with post-transplantation cyclophosphamide for adult T-cell leukaemia/lymphoma.

This study retrospectively compared outcomes of various allogeneic haematopoietic cell transplantation (allo-HCT) platforms in patients with adult T-cell leukaemia/lymphoma. Platforms included human leukocyte antigen (HLA)-haploidentical-related donors using post-transplant cyclophosphamide (PTCY), HLA-matched related donors (MRD), HLA-matched unrelated donors (MUD) and cord blood transplantation (CBT). Patients who underwent their first allo-HCT between 2016 and 2021 were included. Outcomes analysed were overall survival (OS), relapse and non-relapse mortality (NRM). Seven hundred patients were included (PTCY, n = 121; MRD, n = 91; MUD, n = 160; CBT, n = 328). With a median follow-up of 794 days for survivors, 2-year OS was 48.1% (PTCY), 48.8% (MRD), 48.4% (MUD) and 34.6% (CBT); the respective 2-year cumulative incidence of relapse was 37.1%, 47.5%, 33.9% and 45.1% and that of NRM was 24.2%, 19.8%, 24.7% and 27.3%. PTCY was associated with delayed platelet engraftment relative to MRD and MUD. There was no increase in the incidence of severe acute or chronic graft-versus-host disease. In the PTCY group, poor performance status was a significant predictor of inferior OS, and infused CD34+ cell numbers of less than 5 × 106/kg were associated with delayed neutrophil and platelet engraftment. These results suggest that allo-HCT with PTCY is a safe and effective platform for patients with adult T-cell leukaemia/lymphoma.

A girl with a novel nonsense mutation in Chediak-Higashi syndrome was relieved successfully by treatment with HCST and UCBT: a case report.

Chediak-Higashi syndrome (CHS) is a life-threatening autosomal recessive immunodeficiency disease presenting with recurrent infections, hypopigmentation, progressive neurodegeneration, and hemophagocytic lymphohistiocytosis (HLH), known as the accelerated stage. Two-thirds of patients experience a fatal accelerated phase. CHS is caused by lysosomal transport regulator (LYST) gene mutations. We report the case of CHS, who was born with pale skin and silver hair. Bone marrow aspirate revealed large inclusions in granulocytes, monocytes, and lymphocytes. Genetic analysis revealed a new nonsense mutation in the LYST gene: c.8186G > A (W2729Ter). The child presented with fever, hepatosplenomegaly, and lymphadenectasis. Laboratory tests showed pancytopenia, hypofibrinogenemia, and high serum ferritin, indicating an accelerated phase of CHS. She underwent allogeneic hematopoietic stem cell transplantation (HCST) combined with umbilical cord blood transplantation (UCBT) after HLH-related chemotherapy. The patient has been alive for nine months without recurrence. We have identified a novel nonsense mutation in the LYST gene that correlates with a severe phenotype, and HSCT combined with UCBT is an effective treatment.

A Pilot Study of UM171-Expanded Cord Blood Grafts for Tandem Auto/Allogeneic Hematopoietic Cell Transplant in High and Ultra-High-Risk Myeloma Patients

Multiple myeloma (MM) remains associated with a poor outcome, particularly in patients with advanced disease and high-risk (HR) cytogenetics. To date, the only curative treatment is allogeneic (allo) hematopoietic cell transplantation (HCT), but high incidences of graft versus host disease (GVHD), non-relapse mortality (NRM) and disease progression remain important obstacles. Cord blood (CB) transplantation has been associated with low rates of relapse and chronic (c) GVHD, but its use has declined because of high incidences of infections, severe acute GVHD and high NRM. In other hematologic malignancies, UM171-expanded CB transplants have led to improved outcomes, allowing for the selection of smaller, better HLA-matched units. We aimed to investigate the safety and feasibility of single UM171-expanded single CB unit transplantation in frontline tandem auto/allo HCT for HR/ultra-HR MM patients. Newly diagnosed MM patients ≤ 65 years with an ISS stage II/III and del17p, t4,14, t14,16, t14,20, del1p or +1q, R-ISS 3, ≥ 2 cytogenetic abnormalities, or plasma cell leukemia without a sibling donor and availability of a 5-7/8 matched CB graft with ≥ 0.5 x 105 CD34+/kg and ≥ 1.5 x 107 TNCs/kg were eligible to this phase I/II prospective study (ClinicalTrials.gov NCT03441958). After induction and autologous HCT, patients received a reduced intensity conditioning regimen and were infused with 7-day UM171-expanded CD34+ cells, along with the lymphocytes contained in the CD34-negative fraction. The primary endpoints were feasibility of UM171 expansion, safety, kinetics of engraftment, incidences and maximum grades of acute and cGVHD at 1 and 2 years, assessment of measurable residual disease (MRD) and quality of life (QoL). Between 05/2018 and 11/2021, 20 patients were enrolled. One patient had an unsuccessful CB expansion with UM171, leaving 19 patients with a median age of 56 years. Median CD34+ cell dose infused after expansion was 4.62 x 106/kg (range: 0.79-5.76). Median times to achieve absolute neutrophil counts of 0.1 and 0.5 x 109/L were D+6 and D+10.5; median time to reach ≥ 20 x 109/L platelets was D+36. Full donor chimerism was achieved in all cell lineages by D+120 in recipients of reduced intensity conditioning. Cumulative incidences of grade II-IV, grade III-IV acute GVHD and moderate/severe cGVHD at 12 months were 68.4% (95% CI: 46-90), 5.3% (95% CI: 0-16%), and 10.5% (95% CI: 0-25%), respectively. With a median follow-up of 2.9 years (range: 0.46-5.3), cumulative incidences of relapse, PFS, OS and NRM at 3 years were 36.8% (95% CI: 14-59), 47.4% (95% CI: 29-76), 68.4% (95% CI: 50-93) and 15.8% (95%CI: 0-33), respectively. Median time to complete immunosuppression discontinuation was D+238. No unexpected adverse events were observed. Only one of 7 patients alive at 2 years with negative MRD at transplant has relapsed. Non-relapsing patients had a QoL after transplant similar to the general population. UM171-expanded CB transplant in HR/ultra-HR myeloma patients is feasible and allows the use of single CB units with a low risk of cGVHD. Patients with negative pre-transplant MRD might benefit most from a UM171-expanded CB transplant.

Longitudinal outcome over four decades of allogeneic stem cell transplantation: a single center experience.

This 45-year study (1978-2022) at a single institution evaluated HSCT outcomes and complications, emphasizing recent advances, with to provide insights into HSCT's evolving field and ongoing efforts to enhance patient outcomes. Involving 1707 patients, the study revealed an initial phase (1978-1987) with a limited activity that yielded modest outcomes, a nearly three-decade span (1988-2016) with a substantial increase in transplant activity, emphasizing umbilical cord blood transplantation (UCBT) for patients lacking a suitable matched sibling donor. In addition to a gradual increase in recipient age, significant improvement in outcomes emerged in the recent period (2017-2022), marked by UCBT replacement with haploidentical transplants, introduction of PTCY-based GVHD prophylaxis for all type of transplants, and increased use of conditioning regimens with thiotepa, busulfan, and fludarabine. In this period, reductions in GVHD, non-relapse mortality, and relapse rates significantly contributed to improved overall survival, event-free survival, and GVHD-free/relapse-free survival. The study identified specific factors, including GVHD prophylaxis and donor selection changes, associated with these positive trends. This four-decade study provides a unique perspective on allogeneic HSCT, showcasing the dynamic evolution of transplantation practices and their impact on outcomes, offering valuable insights for personalized treatment approaches and emphasizing continual innovation in this critical therapeutic modality.

Impact of donor type on the outcomes of acute graft versus host disease to systemic corticosteroid therapy.

Systemic corticosteroid therapy is a well-established first-line treatment for grades II-IV acute graft-versus-host disease (aGVHD). Recently, several developments have occurred, including the introduction of transplantation from human leukocyte antigen (HLA) haploidentical donors using post-transplant cyclophosphamide (PTCY-Haplo), and improvements in prognosis after cord blood transplantation (CBT) in Japan. This study aimed to analyze the association between donor sources and outcomes in patients with aGVHD. Our study included 2732 patients who developed grades II-IV aGVHD, and were treated with systemic corticosteroids. We compared HLA-matched related donors (MRD), HLA-matched unrelated donors (MUD), PTCY-Haplo, and CBT. We set endpoint as response rate, 1-year cumulative incidence of non-relapse mortality (NRM), and overall survival (OS). The adjusted odds ratios for a complete response (CR) were 0.99 (95% confidence interval [CI]: 0.74-1.31, P = 0.925) for MUD, 2.08 (95% CI: 1.35-3.25, P = 0.001) for PTCY-Haplo, and 1.08 (95% CI: 0.83-1.41, P = 0.550) for CBT compared with MRD. A significant increase in response rates for PTCY were only found in a single-organ involvement. No significant association was observed between the donor source and NRM or OS. In conclusion, PTCY-Haplo is associated with a high response rate in patients with a single-organ aGVHD; however, MUD and CBT were not associated with treatment response.

Haploidentical transplantation with post-transplant cyclophosphamide versus single cord blood transplantation in adults with relapsed/refractory non-Hodgkin lymphoma.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for relapsed or refractory non-Hodgkin lymphoma (R/R NHL). Allo-HSCT using post-transplant cyclophosphamide (PTCY-haplo) and umbilical cord blood transplantation (uCBT) are important donor options in the absence of matched related siblings. However, the data comparing these two donor sources in R/R NHL are limited. Using the Japanese nationwide transplantation registry data, we identified 857 patients with R/R NHL, including 169 patients who received PTCY-haplo and 688 who received uCBT for their first allo-HSCT between January 2013 and December 2021; 514 patients (60%) had B-cell lymphoma. More PTCY-haplo recipients received allo-HSCT using a reduced-intensity conditioning regimen in recent years. The 3-year overall survival (OS), progression-free survival (PFS), and graft-versus-host disease (GVHD)-free/relapse-free survival (GRFS) rates in the PTCY-haplo and uCBT groups were 44% versus 39% (P = 0.326), 34% versus 33% (P = 0.660), and 19% versus 23% (P = 0.910), respectively; the adjusted hazard ratios for OS, PFS, and GRFS were 0.89 (95% confidence interval: 0.69-1.15, P = 0.373), 0.98 (0.78-1.22, P = 0.852), and 0.92 (0.83-1.21, P = 0.920), respectively. The PTCY-haplo group showed faster neutrophil and platelet engraftment and a lower incidence of grade III-IV acute GVHD. Thus, PTCY-haplo and uCBT could serve as alternative donor sources in patients with R/R NHL.

Alectinib maintenance therapy following cord blood transplantation for relapsed pediatric anaplastic large cell lymphoma with central nervous system involvement.

Pediatric ALK-positive anaplastic large cell lymphoma is a rare subtype of non-Hodgkin lymphoma, and approximately 30% of patients relapse following treatment with conventional chemotherapy. Alectinib monotherapy has demonstrated excellent activity in relapsed and refractory ALCL, but its role as a maintenance therapy after hematopoietic cell transplantation is unclear. We experienced a relapse case of pediatric ALK-positive ALCL with central nervous system involvement treated with alectinib maintenance therapy following cord blood transplantation. The patient has maintained complete remission for more than 3 years after transplantation. There were no remarkable adverse effects that led to discontinuation of alectinib.

Posttransplant cyclophosphamide versus anti-thymocyte globulin versus combination for graft-versus-host disease prevention in haploidentical transplantation for adult acute myeloid leukemia: A report from the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party.

The optimal choice for graft-versus-host disease (GVHD) prophylaxis in haploidentical stem cell transplantation (haplo-SCT) remains debatable. Posttransplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are two common strategies, but little is known about their combination. Using the European Society for Blood and Marrow Transplantation (EBMT) registry, the authors identified 3649 adult patients with acute myeloid leukemia (AML) who underwent haplo-SCT in complete remission between 2007 and 2021 at 260 EBMT-participating centers who received either PTCy (n=2999), ATG (n=358), or combination prophylaxis (n=292). Cord blood transplants, combined bone marrow and peripheral grafts, and transplants with ex vivo graft manipulation were excluded. Median follow-up was 31.8 months. On multivariate analysis, adjusting for patient age and performance status, disease status at transplant, cytogenetic risk, conditioning intensity, stem cell source, female-to-male graft, and donor and patient CMV status, we present the following. Compared to PTCy, ATG had a higher risk of nonrelapse mortality (hazard ratio [HR], 1.6; p=.003), worse leukemia-free survival (HR, 1.4; p=.002), overall survival (HR,1.49; p=.0009), and GVHD-free and relapse-free survival (HR,1.29; p=.012). The combination of PTCy and ATG, however, led to significantly reduced rates of grade 2-4 (HR, 0.51; p=.0003) and grade 3-4 (HR, 0.5; p=.018) acute GVHD and did not affect any transplant outcomes compared to PTCy without ATG. The authors conclude that ATG alone is a less effective prophylaxis strategy compared to PTCy, however, the combination of PTCy and ATG is superior to either monotherapy. They propose that this combination could be considered a potential new standard of care for GVHD prophylaxis in haplo-SCT for AML.

Levels of C-Reactive Protein and Body Temperature Elevation During Neutropenia Predict Engraftment and Non-Relapse Mortality for Unrelated Single-Unit Cord Blood Transplantation in Adults

Cord blood transplantation (CBT) presents unique challenges related to inflammation during neutropenia, such as mucosal damage, infections, and the potential development of pre-engraftment syndrome or pre-engraftment immune reaction. These factors can contribute to significant inflammation and infection shortly after CBT. However, the effect of severe inflammation during neutropenia, specifically elevated C-reactive protein (CRP) level and body temperature, on post-transplant outcomes after CBT remains unclear. This retrospective study aimed to investigate the association between maximum CRP level, maximum body temperature during neutropenia, and post-transplantation outcomes in adult patients undergoing single-unit CBT. We retrospectively evaluated the impact of maximum CRP level and maximum body temperature during neutropenia on post-transplantation outcomes in adults who underwent single-unit unrelated CBT between 1998 and 2023 at our institution. A total of 336 adult patients were included in this study. The median maximum CRP level before neutrophil recovery was 7.75 mg/dL (interquartile range [IQR], 4.70 to 12.05 mg/dL) at a median of 14 d (IQR, 8 to 16 d). The median maximum body temperature before neutrophil recovery was 39.5°C (IQR, 39.0 to 40.0°C) at a median of 15 d (IQR, 12 to 17 d). In the multivariate analysis, a maximum CRP level≥20 mg/dL was significantly associated with lower neutrophil recovery (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.23 to 0.59; P < .001), lower platelet recovery (HR, 0.28; 95% CI, 0.16 to 0.48; P < .001), and a higher incidence of veno-occlusive disease/sinusoidal obstruction syndrome (HR, 16.42; 95% CI, 4.11 to 65.54; P < .001), which resulted in higher non-relapse mortality (NRM) (HR, 5.16; 95% CI, 2.62 to 10.15; P < .001) and worse overall survival (HR, 2.81; 95% CI, 1.66 to 4.78; P < .001). Similarly, a maximum body temperature≥40.5°C was significantly associated with lower neutrophil recovery (HR, 0.51; 95% CI, 0.33 to 0.79; P = .002), lower platelet recovery (HR, 0.55; 95% CI, 0.38 to 0.79; P = .001), higher incidence of grades III to IV acute GVHD (HR, 2.93; 95% CI, 1.24 to 6.88; P = .013), and extensive chronic GVHD (HR, 2.47; 95% CI, 1.22 to 4.97; P = .011), which resulted in higher NRM (HR, 3.43; 95% CI, 1.53 to 7.67; P = .002). Maximum CRP level and maximum body temperature during neutropenia were significantly associated with lower hematopoietic recovery and higher NRM following single-unit CBT in adults. Further studies are warranted to explore early intervention strategies aimed at preventing severe inflammation and improving post-transplant outcomes in single-unit CBT.

Efficacy and safety of avatrombopag in the treatment of thrombocytopenia after umbilical cord blood transplantation.

Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We conducted a retrospective study to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. Fifty-two patients were given AVA within 30days post-UCBT, and the treatment was continued for more than 7days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5days vs. 38.0days, Z=2.095, P=0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs. 84.5% vs. 80.6%, P<0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P=0.104). Patients who initiated AVA treatment within 14days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14days post-UCBT (96.6% vs. 73.9%, P=0.003). In summary, compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14days post-UCBT).

Fludarabine Melphalan, Reduced-dose Busulfan Versus Fludarabine, Melphalan, Full-dose Busulfan in Patients Receiving Cord Blood Transplantation

BackgroundVarious reduced-intensity conditioning/reduced-toxicity conditioning regimens have been developed for patients receiving allogeneic hematopoietic cell transplantation. The balance between disease relapse and toxicity can be partly dependent on reduced-intensity conditioning/reduced-toxicity conditioning regimens.This retrospective study aimed to compare the nonrelapse mortality, relapse incidence, progression-free survival, and overall survival rates between the fludarabine/melphalan/reduced-dose busulfan (Flu/Mel/Bu2; busulfan at a dose of 6.4 mg/kg intravenously) and fludarabine/melphalan/full-dose busulfan (Flu/Mel/Bu4; busulfan at a dose of 12.8 mg/kg intravenously) regimens in patients receiving umbilical cord blood transplantation (UCBT). MethodEighty-seven adult patients who received the Flu/Mel/Bu2 (n = 45) or Flu/Mel/Bu4 (n = 42) regimen as a conditioning regimen before UCBT at our institution between January 2013 and December 2022 were included in this study. ResultsThere were no significant differences in terms of clinical outcomes including nonrelapse mortality, relapse incidence, progression-free survival, and overall survival rates between the two regimens. Further, even in higher risk patients classified according to the Refined Disease Risk Index, the Flu/Mel/Bu2 regimen was comparable to the Flu/Mel/Bu4 regimen. ConclusionThe novel Flu/Mel/Bu2 regimen could be applied in clinical settings as it can be tolerated and effective in older patients.

Long-term engrafting multilineage hematopoietic cells differentiated from human induced pluripotent stem cells.

Hematopoietic stem cells (HSCs) derived from human induced pluripotent stem cells (iPS cells) have important biomedical applications. We identified differentiation conditions that generate HSCs defined by robust long-term multilineage engraftment in immune-deficient NOD,B6.Prkdcscid Il2rgtm1Wjl/SzJ KitW41/W41 mice. We guided differentiating iPS cells, as embryoid bodies in a defined culture medium supplemented with retinyl acetate, through HOXA-patterned mesoderm to hemogenic endothelium specified by bone morphogenetic protein 4 and vascular endothelial growth factor (VEGF). Removal of VEGF facilitated an efficient endothelial-to-hematopoietic transition, evidenced by release into the culture medium of CD34+ blood cells, which were cryopreserved. Intravenous transplantation of two million thawed CD34+ cells differentiated from four independent iPS cell lines produced multilineage bone marrow engraftment in 25-50% of immune-deficient recipient mice. These functionally defined, multipotent CD34+ hematopoietic cells, designated iPS cell-derived HSCs (iHSCs), produced levels of engraftment similar to those achieved following umbilical cord blood transplantation. Our study provides a step toward the goal of generating HSCs for clinical translation.

Transplant Outcomes in Myelofibrosis: Impact of Donor Type (Cord Blood Grafts Supported by CD34+ selected Cells [Haplo-Cord] Versus Matched Donors)

BackgroundDespite the established potentially curative role of allogeneic hematopoietic cell transplantation (alloHCT) in managing MF, the choice of alternative donors for patients lacking matched donors remains a challenge, and the optimal graft source in this disease entity continues to be an ongoing debate. ObjectivesWe aimed to evaluate the impact of donor type: umbilical cord blood transplant supported CD34+ haploidentical donor (haplo-cord) vs adult matched related donor (MRD) and matched unrelated donor (MUD) in 40 adult patients with primary or secondary MF, including those progressing to accelerated phase (AP) or blast phase (BP), who underwent their first allo-HCT. The primary objective of this study was to analyze the impact of stem cell source on primary endpoints of overall survival (OS), graft versus host disease (GVHD) and non-relapse mortality (NRM). ResultsMedian follow-up for all alive patients was 53 months (range 0.3-63 months). Nine patients (22.5%) underwent an MRD allo-HCT, 15 patients (37.5%) underwent a MUD allo-HCT, and 16 patients (40%) underwent a haplo-cord allo-HCT. Four patients died without neutrophil engraftment: 3 (19%) in haplo-cord group and one (4%) in MRD/MUD group. The cumulative incidence of ANC engraftment by day 60 was 80% (95%CI 45-94) in the haplo-cord group and 92% (95%CI 65-98) in the MRD/MUD group (p=0.09). The cumulative incidence of platelet engraftment by day 60 was 59% (95%CI 27-81) in haplo-cord group and 75% (95%CI 51-88) in MRD/MUD group (p=0.4). OS was 62% at 1 year (95%CI 49-79) and 34% at 3 years (95%CI 21-55). The 3-yr OS was similar between the haplo-cord group and the MRD/MUD (37% vs 32%, p=0.9). The 1-yr OS for accelerated/blast phase AP/BP patients was 50% (95%CI 27-93) in the haplo-cord group, compared to 40% (95%CI 19-86) in the MRD/MUD. The 1-yr OS for chronic phase CP patients was 83% (95%CI 58-100) in the haplo-cord group, compared to 79% (95%CI 60-100) in the MRD/MUD group. The cumulative incidence of relapse at 3 years in the haplo-cord group was 13% (95%CI 1.8-34), and in the MRD/MUD group was 28% (95%CI 10-49) (p=0.36). 1-yr non-relapse mortality (NRM) was 38% (95%CI 15-61) in the haplo-cord group and 33% (95%CI 15-52) in the MRD/MUD group. 3-yr NRM was 48% (95%CI 19-72) in the haplo-cord group and 54% (95%CI 29-73) in MRD/MUD group(p=0.95). ConclusionWe showed no significant difference in OS, relapse, and NRM outcomes after haplo-cord transplant compared to adult matched donors’ grafts (MRD or MUD) in MF patients. However, there were more graft failures in patients transplanted with a haplo-cord transplants and delayed engraftments with inadequate haplo myeloid bridges. Despite the small sample size in our study, considering our findings and the availability of other alternative donors, using haplo-cord platforms may no longer be justified for myelofibrosis unless the UCB engraftment dynamics can be optimized.

Higher survival following transplantation with a mismatched unrelated donor with posttransplant cyclophosphamide-based graft-versus-host disease prophylaxis than with double unit umbilical cord blood in patients with acute myeloid leukemia in first complete remission: A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

The best donor option for acute myeloid leukemia (AML) patients lacking an HLA-matched donor has remained intensively debated. We herein report the results of a large retrospective registry study comparing hematopoietic cell transplantation (HCT) outcomes between double-unit umbilical cord blood transplantation (dCBT, n = 209) versus 9/10 HLA-matched unrelated donor (UD) with posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis (UD 9/10, n = 270) in patients with AML in first complete remission (CR1). Inclusion criteria consisted of adult patient, AML in CR1 at transplantation, either peripheral blood stem cells (PBSC) from UD 9/10 with PTCy as GVHD prophylaxis or dCBT without PTCy, transplantation between 2013 and 2021, and no in vivo T-cell depletion. The 180-day cumulative incidence of grade II-IV acute GVHD was 29% in UD 9/10 versus 44% in dCBT recipients (p = .001). After adjustment for covariates, dCBT recipients had a higher non-relapse mortality (HR = 2.35, 95% CI: 1.23-4.48; p = .01), comparable relapse incidence (HR = 1.12, 95% CI: 0.67-1.86; p = .66), lower leukemia-free survival (HR = 1.5, 95% CI: 1.01-2.23; p = .047), and lower overall survival (HR = 1.66, 95% CI: 1.08-2.55; p = .02) compared with patients receiving UD 9/10 HCT. In summary, our results suggest that transplantation outcomes are better with UD 9/10 with PTCy-based GVHD prophylaxis than with dCBT for AML patients in CR1. These data might support the use of UD 9/10 with PTCy-based GVHD prophylaxis over dCBT in AML patients lacking an HLA-matched donor.

Prognostic Value of the Pretransplant Fibrosis-4 Index on Non-Relapse and Overall Mortality following Unrelated Single-Unit Cord Blood Transplantation in Adults

Introduction: The fibrosis-4 (FIB-4) index is a noninvasive marker of liver fibrosis. The FIB-4 index predicts poor outcomes in patients with hepatic and non-hepatic diseases. However, the association of the FIB-4 index with mortality and liver-related clinical outcomes following cord blood transplantation (CBT) is unclear. Methods: We retrospectively evaluated the impact of the pretransplant FIB-4 index on outcomes in 336 adults following single-unit unrelated CBT at our institution. Results: In multivariate analyses, when the FIB-4 index <1.3 group was used as the reference, non-relapse mortality was significantly higher in the FIB-4 index 1.3–2.67 (hazard ratio [HR], 2.51; 95% confidence interval [CI], 1.19–5.30) and FIB-4 index >2.67 (HR, 2.34; 95% CI, 1.12–4.90) groups. Overall mortality was significantly higher in the FIB-4 index >2.67 group (HR, 1.66; 95% CI, 1.00–2.73), but with only marginal significance in the FIB-4 index 1.3–2.67 group (HR, 1.59; 95% CI, 0.96–2.64). Hematopoietic recovery, acute and chronic graft-versus-host disease of the liver, and veno-occlusive disease/sinusoidal obstruction syndrome were not associated with the pretransplant FIB-4 index. Conclusion: The pretransplant FIB-4 index is accurate and useful in predicting mortality in adult patients undergoing single-unit unrelated CBT.

Abstract 14: Contribution of US Public Cord Blood Banking to Improved Engraftment and Survival after Allogeneic Cord Blood Transplantation (CBT)

Abstract 14: Contribution of US Public Cord Blood Banking to Improved Engraftment and Survival after Allogeneic Cord Blood Transplantation (CBT)

Abstract 25: During CB Transplant in MRD-Positive AML, Relapse is Usually Early, is Reduced by Acute GVHD and is Influenced by Ciclosporin Exposure: A Multicenter National Experience

Abstract 25: During CB Transplant in MRD-Positive AML, Relapse is Usually Early, is Reduced by Acute GVHD and is Influenced by Ciclosporin Exposure: A Multicenter National Experience

The Clinical Influence of Complete Remission With Incomplete Count Recovery (CRi) on Single-Unit Unrelated Cord Blood Transplantation in Patients With Acute Leukemia

Recent evidence has indicated that measurable residual disease (MRD) markedly affects the prognosis of patients with acute leukemia post-transplantation. However, the prognostic relevance of complete remission with incomplete count recovery (CRi) before transplantation has not been extensively explored. In this single-center, longitudinal study, we assessed the outcomes of 466 MRD-negative acute leukemia patients who underwent single-unit unrelated cord blood transplantation (sUCBT), including 117 patients with CRi. We observed that acute myeloid leukemia (AML) patients with CRi had a significantly lower cumulative incidence of both neutrophil (90.8% versus 96.5%) and platelet engraftment (67.2% versus 85.3%) and experienced increased transplant-related mortality (TRM) (100-day TRM: 14.2% versus 5.3%; 1-year TRM: 20.6% versus 11.3%; P = .024 and .063, respectively), mainly due to infection-related deaths, compared to those in complete remission (CR). Multivariate analysis revealed that CRi was an independent adverse predictor of both neutrophil and platelet engraftment and increased 100-day TRM in AML patients. However, CRi status did not affect relapse or reduce 5-year overall survival (OS), leukemia-free survival (LFS), or GVHD-free relapse-free survival (GRFS) in the AML cohort. Conversely, for patients with acute lymphoblastic leukemia (ALL), CRi did not impact engraftment, TRM, relapse or survival after sUCBT. Our findings underscore that CRi status before sUCBT portends poorer engraftment outcomes and a greater TRM in AML patients, although it does not significantly affect the prognosis of ALL patients.

Haploidentical versus Cord Blood Transplantation in Pediatric AML. A Retrospective Outcome Analysis on Behalf of the Pediatric Subcommittee of GETH (Grupo Español de Trasplante Hematopoyético)

Haploidentical stem cell transplantation (Haplo-SCT) and cord blood transplantation (CBT) are both effective alternative treatments in patients suffering from acute myeloid leukemia (AML) and lacking a matched HLA donor. In the last years, many centers have abandoned CBT procedures mostly due to concern about poorer immune recovery compared with Haplo-SCT. We conducted a retrospective multicenter study comparing the outcomes using both alternative approaches in AML. A total of 122 transplants (86 Haplo-SCTs and 36 CBTs) from 12 Spanish centers were collected from 2007 to 2021. Median age at hematopoietic stem cell transplantation (HSCT) was 7 years (0.4-20). Thirty-nine patients (31.9%) showed positive minimal residual disease (MRD) at HSCT and a previous HSCT was performed in 37 patients (30.3%). The median infused cellularity was 14.4 × 106/kg CD34+ cells (6.0-22.07) for Haplo-SCT and 4.74 × 105/kg CD34+ cells (0.8-9.4) for CBT. Median time to neutrophil engraftment was 14 days (7-44) for Haplo-SCT and 17 days (8-29) for CBT (P = .03). The median time to platelet engraftment was 14 days (6-70) for Haplo-SCT and 43 days (10-151) for CBT (P < .001). Graft rejection was observed in 13 Haplo-SCTs (15%) and in 6 CBTs (16%). The cumulative incidence of acute graft versus host disease (GvHD) grades II-IV was 54% and 51% for Haplo-SCT and CBT, respectively (P = .50). The cumulative incidence of severe acute GvHD (grades III-IV) was 22% for Haplo-SCT and 25% for CBT (P = .90). There was a tendency to a higher risk of chronic GvHD in the Haplo-SCT group being the cumulative incidence of 30% for Haplo-SCT and 12% for CBT (P = .09). The cumulative incidence of relapse was 28% and 20% for Haplo-SCT and CBT, respectively (P = .60). We did not observe statistically significant differences in outcome measures between Haplo-SCT and CBT procedures: 5-year overall survival (OS) was 64% versus 57% (P = .50), 5-year disease-free survival (DFS) 58% versus 57% (P = .80), GvHD-free and relapse-free survival (GFRFS) 41% versus 54% (P = .30), and cumulative incidence of transplant-related mortality (TRM) 14% versus 15% (P = .80), respectively. In the multivariate analysis, MRD positivity and a disease status >CR1 at the time of HSCT were significantly associated with poorer outcomes (P < .05). In conclusion, our study supports that both haploidentical and cord blood transplantation show comparable outcomes in pediatric AML patients. We obtained comparable survival rates, although CBT showed a trend to lower rates of chronic GvHD and higher GFRFS, demonstrating that it should still be considered a valuable option, particularly for pediatric patients.

Recipient IL-17A polymorphism rs2275913 is associated with acute graft-versus-host disease after single-unit cord blood transplantation

BackgroundInterleukin-17 (IL-17) is elevated in human inflammatory and autoimmune diseases. The polymorphism in the promoter region of the IL-17 A gene is associated with susceptibility to several inflammatory diseases, including acute graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation from adult donors. However, the impacts of IL-17 A polymorphism on cord blood transplantation (CBT) outcomes remain unclear. ObjectiveThe objective of this study was to assess the impact of IL-17 A polymorphism rs2275913 on GVHD, survival, relapse, non-relapse mortality (NRM), and hematopoietic recovery after CBT. Study DesignWe conducted a retrospective analysis of data from adult patients who underwent single-unit CBT at our institution from January 2005 to March 2023 for whose recipient or donor DNA samples were available. IL-17 A genotyping was performed using real-time polymerase chain reaction with the TaqMan® SNP genotyping assay for rs2275913. ResultsA total of 158 recipients and 136 donors were evaluated in this study. Multivariate analysis showed that rs2275913 GA or AA recipients were associated with increased risk of grades II to IV acute GVHD compared to GG recipients (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.00–2.13; P = 0.047). Serum IL-17 A levels at eight weeks were significantly higher in rs2275913 GA or AA recipients compared to GG. The rs2275913 polymorphism did not affect survival, relapse, NRM, or hematopoietic recovery after single-unit CBT. ConclusionOur data showed recipient IL-17 A polymorphism rs2275913 was associated with the risk of grade II to IV acute GVHD in adults undergoing single-unit CBT. However, the rs2275913 polymorphism in recipients and donors did not affect survival or relapse. Thus, the polymorphism of IL-17 A rs2275913 in recipients might predict the risk of acute GVHD after single-unit CBT.